Target
Validation Information |
TTD ID | TTDC00292 |
Target Name | Alpha-1A adrenergic receptor |
Type of Target | Clinical trial target |
Drug Potency against Target | Dutasteride & tamsulosin |  | IC50 = 6 nM | [1] |
WAY-100135 |  | IC50 = 1490 nM | [2] |
ATC-0175 |  | IC50 = 300 nM | [3] |
Siramesine |  | IC50 = 330 nM | [4] |
ISOCLOZAPINE |  | IC50 = 64 nM | [5] |
ABANOQUIL |  | Ki = 0.03 nM | [6] |
SILODOSIN |  | Ki = 0.036 nM | [7] |
(+)-NIGULDIPINE |  | Ki = 0.16 nM | [7] |
SNAP-7915 |  | Ki = 0.17 nM | [7] |
(-)-SNAP-5089 |  | Ki = 0.18 nM | [7] |
MAZAPERTINE |  | Ki = 0.2 nM | [8] |
SNAP-6201 |  | Ki = 0.2 nM | [7] |
A-131701 |  | Ki = 0.22 nM | [7] |
RS-100329 |  | Ki = 0.25 nM | [7] |
WB-4101 |  | Ki = 0.35 nM | [6] |
L-771688 |  | Ki = 0.36 nM | [7] |
(-)-SNAP-5399;SNAP-5399 |  | Ki = 0.4 nM | [7] |
RS-17053 |  | Ki = 0.6 nM | [7] |
RWJ-69736 |  | Ki = 0.65 nM | [7] |
OCTOCLOTHEPIN |  | Ki = 0.66 nM | [9] |
FLUANISONE |  | Ki = 0.87 nM | [10] |
UPIDOSIN |  | Ki = 1 nM | [7] |
Ro-700004;RS-100975 |  | Ki = 1.3 nM | [7] |
SNAP-5089 |  | Ki = 1.3 nM | [11] |
TIOSPIRONE |  | Ki = 1.5 nM | [12] |
NIGULDIPINE |  | Ki = 1.8 nM | [11] |
SNAP-5150 |  | Ki = 1.9 nM | [7] |
(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine |  | Ki = 11000 nM | [13] |
Imidazolidin-2-ylidene-quinoxalin-6-yl-amine |  | Ki = 11000 nM | [14] |
MEDETOMIDINE |  | Ki = 1102 nM | [15] |
R-226161 |  | Ki = 125 nM | [16] |
SNAP-8719 |  | Ki = 1400 nM | [17] |
5-Bromo-8-piperazin-1-yl-imidazo[1,2-a]pyrazine |  | Ki = 1490 nM | [18] |
4-(3-Hydroxy-piperidin-3-yl)-benzene-1,2-diol |  | Ki = 15000 nM | [19] |
N-(5-Bromo-quinoxalin-6-yl)-guanidine |  | Ki = 17000 nM | [14] |
4-(1-Naphthalen-1-yl-vinyl)-1H-imidazole |  | Ki = 1734 nM | [20] |
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one |  | Ki = 18 nM | [21] |
SNAP-94847 |  | Ki = 180 nM | [22] |
(+/-)-nantenine |  | Ki = 2 nM | [23] |
A-119637 |  | Ki = 2.6 nM | [7] |
RWJ-68157 |  | Ki = 22 nM | [7] |
1-Pyridin-2-yl-piperazine |  | Ki = 2400 nM | [24] |
Imidazolidin-2-ylidene-o-tolyl-amine |  | Ki = 2500 nM | [14] |
RX-821002 |  | Ki = 27 nM | [25] |
CORYNANTHEINE |  | Ki = 29 nM | [7] |
BMY-7378 |  | Ki = 290 nM | [17] |
NAFTOPIDIL |  | Ki = 3.7 nM | [7] |
8-Piperazin-1-yl-imidazo[1,2-a]pyrazine |  | Ki = 3100 nM | [18] |
4-(3,4-Dihydro-1H-isoquinolin-2-yl)-quinoline |  | Ki = 3200 nM | [26] |
BP-897 |  | Ki = 33 nM | [27] |
SK&F-104078;SK-104078 |  | Ki = 33 nM | [11] |
SK&F-105854;SK-105854 |  | Ki = 3300 nM | [7] |
4-Benzo[b]thiophen-4-yl-1H-imidazole |  | Ki = 343 nM | [28] |
sunepitron |  | Ki = 35 nM | [29] |
1-(2-Methoxy-phenyl)-piperazine |  | Ki = 3508 nM | [30] |
SK&F-104856;SK-104856 |  | Ki = 36 nM | [11] |
4-((E)-1-Naphthalen-1-yl-propenyl)-1H-imidazole |  | Ki = 387 nM | [20] |
A-123189 |  | Ki = 4.2 nM | [7] |
SNAP-5036 |  | Ki = 4.4 nM | [7] |
1',2',3',6'-Tetrahydro-[2,4']bipyridinyl |  | Ki = 4000 nM | [24] |
RS-513815 |  | Ki = 41 nM | [7] |
L-765314 |  | Ki = 420 nM | [7] |
SK&F-86466;SK-86466 |  | Ki = 449 nM | [11] |
AGN-193080 |  | Ki = 470 nM | [14] |
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine |  | Ki = 490 nM | [24] |
A-315456 |  | Ki = 490 nM | [7] |
Ro-11-04253 |  | Ki = 5 nM | [7] |
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole |  | Ki = 536 nM | [15] |
4-(2,3-Dihydro-1H-phenalen-1-yl)-1H-imidazole |  | Ki = 55 nM | [20] |
4-((Z)-1-Naphthalen-1-yl-propenyl)-1H-imidazole |  | Ki = 57 nM | [20] |
4-(1-Naphthalen-1-yl-propyl)-1H-imidazole |  | Ki = 574 nM | [20] |
SK&F-106686;SK-106686 |  | Ki = 58 nM | [11] |
2-Pyridin-4-yl-1,2,3,4-tetrahydro-isoquinoline |  | Ki = 5800 nM | [26] |
RWJ-68141 |  | Ki = 59 nM | [7] |
(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine |  | Ki = 6000 nM | [13] |
UH-301 |  | Ki = 6080 nM | [2] |
4-(4-Isopropyl-morpholin-2-yl)-benzene-1,2-diol |  | Ki = 6700 nM | [19] |
SPIPERONE |  | Ki = 7.9 nM | [7] |
1-(2-Chloro-phenyl)-piperazine |  | Ki = 710 nM | [30] |
4-(4-Methyl-indan-1-yl)-1H-imidazole |  | Ki = 73 nM | [31] |
4-Morpholin-2-yl-benzene-1,2-diol |  | Ki = 7400 nM | [19] |
RWJ-25730 |  | Ki = 8.2 nM | [8] |
AGN-192172 |  | Ki = 8900 nM | [14] |
RWJ-38063 |  | Ki = 9.3 nM | [7] |
2-(4-tert-Butyl-phenyl)-4,5-dihydro-1H-imidazole |  | Ki = 91 nM | [32] |
LEVONORDEFRIN |  | Ki = 9221 nM | [20] |
Action against Disease Model | Alfuzosin |  | Alfuzosin significantly prolonged action potential duration (APD)(60) in rabbit Purkinje fibers (p < 0.05) and QT in isolated rabbit hearts (p < 0.05) at the clinically relevant concentration of 300 nM. In man, the QT interval corrected with Fridericia's formula increased 7.7 ms, which exceeds the 5.0-ms threshold for a positive TCQS. Effects on hK(v)11.1, hK(v)4.3, and hK(v)7.1/hKCNE1 potassi uM currents and calci uM current were not involved. At 300 nM, approximately 30x C(max), alfuzosin significantly increased whole-cell peak sodi uM (hNa(v)1.5) current (p < 0.05), increased the probability of late hNa(v)1.5 single-channel openings, and significantly shortened the slow time constant for recovery from inactivation. | [33] |
The Effect of Target Knockout, Knockdown or Genetic Variations | Alpha 1A-AR knockout mice: cardiac development is normal,cardiac function has decreased contraction and pressor response is decreased to PE | [34] |
Ref 1 | Prostate. 2004 Feb 1;58(2):130-44.Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. To Reference |
Ref 2 | J Med Chem. 1997 Apr 11;40(8):1252-7.N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines: synthesis and wide range of antagonism at the human 5-HT1A receptor. To Reference |
Ref 3 | Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. Epub 2009 Sep 6.Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation. To Reference |
Ref 4 | J Med Chem. 1995 May 26;38(11):1998-2008.Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 1. 3-(omega-aminoalkyl)-1H-indoles. To Reference |
Ref 5 | J Med Chem. 1997 Dec 5;40(25):4146-53.Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine: identification of a novel atypical neuroleptic. To Reference |
Ref 6 | J Med Chem. 1995 Sep 1;38(18):3415-44.Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. To Reference |
Ref 7 | Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. To Reference |
Ref 8 | J Med Chem. 1994 Apr 15;37(8):1060-2.A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. To Reference |
Ref 9 | J Med Chem. 2010 Oct 14;53(19):7021-34.Exploring the neuroleptic substituent in octoclothepin: potential ligands for positron emission tomography with subnanomolar affinity for ¦Á(1)-adrenoceptors. To Reference |
Ref 10 | J Med Chem. 1987 Nov;30(11):2099-104.2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1. To Reference |
Ref 11 | J Med Chem. 1995 Sep 15;38(19):3681-716.Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. To Reference |
Ref 12 | J Med Chem. 1996 Jan 5;39(1):143-8.3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. To Reference |
Ref 13 | J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. To Reference |
Ref 14 | Bioorg. Med. Chem. Lett. 5(15):1745-1750 (1995) To Reference |
Ref 15 | J Med Chem. 1994 Jul 22;37(15):2328-33.A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic receptors. To Reference |
Ref 16 | Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. To Reference |
Ref 17 | J Med Chem. 2005 Apr 21;48(8):3076-9.Synthesis and structure-activity relationship of fluoro analogues of 8-{2-[4-(4-methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as selective alpha(1d)-adrenergic receptor antagonists. To Reference |
Ref 18 | J Med Chem. 1992 Oct 16;35(21):3845-57.Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines. To Reference |
Ref 19 | J Med Chem. 1992 Mar 20;35(6):1009-18.Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors. To Reference |
Ref 20 | J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine. To Reference |
Ref 21 | J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference |
Ref 22 | J Med Chem. 2007 Aug 9;50(16):3883-90.Synthesis and SAR investigations for novel melanin-concentrating hormone 1 receptor (MCH1) antagonists part 2: A hybrid strategy combining key fragments of HTS hits. To Reference |
Ref 23 | Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. To Reference |
Ref 24 | J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. To Reference |
Ref 25 | J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. To Reference |
Ref 26 | Bioorg Med Chem Lett. 2003 May 19;13(10):1759-62.4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists. To Reference |
Ref 27 | J Med Chem. 2003 Aug 28;46(18):3822-39.Synthesis and pharmacological evaluation of potent and highly selective D3 receptor ligands: inhibition of cocaine-seeking behavior and the role of dopamine D3/D2 receptors. To Reference |
Ref 28 | J Med Chem. 2000 Mar 9;43(5):765-8.alpha(2) Adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene [corrected] as a high-affinity ligand for the alpha(2D) adrenergic receptor. To Reference |
Ref 29 | J Med Chem. 2006 Jun 1;49(11):3116-35.An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. To Reference |
Ref 30 | J Med Chem. 1991 Jun;34(6):1850-4.Pyrimido[5,4-b]indole derivatives. 1. A new class of potent and selective alpha 1 adrenoceptor ligands. To Reference |
Ref 31 | J Med Chem. 1997 Sep 12;40(19):3014-24.Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potential binding interactions with alpha 2-adrenoceptors involving a "methyl pocket". To Reference |
Ref 32 | Bioorg Med Chem Lett. 2004 Sep 20;14(18):4697-9.2-(Anilino)imidazolines and 2-(benzyl)imidazoline derivatives as h5-HT1D serotonin receptor ligands. To Reference |
Ref 33 | J Pharmacol Exp Ther. 2008 Feb;324(2):427-33. Epub 2007 Nov 6.Alfuzosin delays cardiac repolarization by a novel mechanism. To Reference |
Ref 34 | Life Sci. 2002 Sep 27;71(19):2207-15.Transgenic studies of alpha(1)-adrenergic receptor subtype function. To Reference |